Recent Progress in Iridium-Catalyzed Enantioselective Hydrogenation: Tetrasubstituted Olefins and Polyenes

Iridium-catalyzed enantioselective hydrogenation has become the method of choice to convert prochiral unfunctionalized olefins to optically active compounds. Recently, we reported on applications giving access to more than one stereocenter in a single hydrogenation step. In this account we present recent developments in the hydrogenation of tetrasubstituted unfunctionalized olefins and isoprenoid polyenes, which allow the generation of two stereocenters in a single hydrogenation step

Artificial intelligence-based non-invasive tumor segmentation, grade stratification and prognosis prediction for clear-cell renal-cell carcinoma

Due to the complicated histopathological characteristics of clear-cell renal-cell carcinoma (ccRCC), non-invasive prognosis before operative treatment is crucial in selecting the appropriate treatment. A total of 126 345 computerized tomography (CT) images from four independent patient cohorts were included for analysis in this study. We propose a V Bottleneck multi-resolution and focus-organ network (VB-MrFo-Net) using a cascade framework for deep learning analysis. The VB-MrFo-Net achieved better performance than VB-Net in tumor segmentation, with a Dice score of 0.87. The nuclear-grade prediction model performed best in the logistic regression classifier, with area under curve values from 0.782 to 0.746. Survival analysis revealed that our prediction model could significantly distinguish patients with high survival risk, with a hazard ratio (HR) of 2.49 [95% confidence interval (CI): 1.13-5.45, P = 0.023] in the General cohort. Excellent performance had also been verified in the Cancer Genome Atlas cohort, the Clinical Proteomic Tumor Analysis Consortium cohort, and the Kidney Tumor Segmentation Challenge cohort, with HRs of 2.77 (95%CI: 1.58-4.84, P = 0.0019), 3.83 (95%CI: 1.22-11.96, P = 0.029), and 2.80 (95%CI: 1.05-7.47, P = 0.025), respectively. In conclusion, we propose a novel VB-MrFo-Net for the renal tumor segmentation and automatic diagnosis of ccRCC. The risk stratification model could accurately distinguish patients with high tumor grade and high survival risk based on non-invasive CT images before surgical treatments, which could provide practical advice for deciding treatment options.</p

Organocatalytic Asymmetric Cycloaddition Reaction of Ketenes

National Natural Science Foundation of China [20902075]; Natural Science Foundation of Fujian Province [2009J05037]; Research Fund for the Doctoral Program of Higher Education of China [20090121120007]; Scientific Research Foundation for the Returned Overseas Chinese Scholars, State Education MinistryIn this review, organocatalytic asymmetric [2+2] and [4+2] cycloaddition reactions of ketenes are summarized with emphasis on the selectivities and mechanisms of different catalysts

Progress on the total synthesis of natural products in China: From 2006 to 2010

This paper summarizes the progress on the total syntheses of natural products accomplished in mainland China during the period from 2006 to 2010. The overview focuses on the first total synthesis of natural products of contemporary interest including alkaloids, cyclopeptides and cyclic depsipeptides, macrolides, terpenoids and steroids, saponins and glycosides. The development of novel synthetic strategies and methodologies, and application of new selective synthetic methods in the total syntheses of natural products are included as well.National Natural Science Foundation of China [20832005, 21072160, 20902075]; National Basic Research Program (973 Program) of China [2010CB833200]; Natural Science Foundation of Fujian Province of China [2009J05037]; Specialized Research Fund for the Doctoral Program of Higher Education [20090121120007]; Scientific Research Foundation for the Returned Overseas Chinese Scholars, Ministry of Education of Chin

Identification of QTLs and candidate genes for rice seed germinability under low temperature using high‐density genetic mapping and RNA‐seq

Abstract Reduced temperatures during germination adversely affect rice (Oryza sativa L.) production. Little is known, however, of the genes or genetic loci involved. Here, QTLs were investigated in a recombinant inbred line (RIL) resulting from a 02428 (japonica)‐YZX (indica) cross. The phenotypes of the cultivars differ significantly when exposed to low temperatures during germination. Mapping with a high‐density bin map identified 11 loci associated with low‐temperature germination of which loci 2 and 4 were identified by multiple traits over two seasons. Locus 2 was a major genetic locus, explaining 22.36% of phenotypic variation. The haplotype results showed that the pyramiding of favorable alleles of these two loci was beneficial to improving the rice seeds' low‐temperature germinability. RNA‐seq analysis was performed on the second day of germination at low temperature for both parents. Three DGEs (Os03g0119800, Os03g0120900, and Os03g0121300) were obtained for locus 2 and were confirmed as the most likely candidates by qRT‐PCR verification, gene sequence alignment, and haplotype analysis. Collectively, these quantitative trait loci and candidate genes may be valuable for the breeding of cold‐tolerant rice lines as well as broadening our knowledge of the genetics underlying germination at low temperatures

A novel and versatile method for the enantioselective syntheses of tropane alkaloids

National Basic Research Program of China (973 Program) [2010CB833200]; National Natural Science Foundation of China [21072160, 21332007]; Program for Changjiang Scholars and Innovative Research Team at the University of the MOEA full account of the novel and flexible approach to hydroxylated 8-azabicyclo[3,2,1]octan-3-ones and 9-azabicyclo[3,3,1] nonan-3-ones is presented. Using keto-lactams as the starting materials, this two-step method consists of silyl enol ether formation with TBDMSOTf, lactam activation with Tf2O/DTBMP, and halide-promoted cyclization. Radical dechlorination of the resulting 1-halotropan-3-ones led to the corresponding hydroxylated tropan-3-ones, which can be hydrogenated to yield 3 alpha,6 beta-dihydroxytropanes. Starting from optically active keto-lactams, the method has been applied to the enantioselective syntheses of (+)-(1S,3S,5R,65)-pervilleine C (6), (+)-(1S,3R,5S,6R)-valeroidine (3), (+)-(1S,3S,5R,6,9)-dibenzoyloxytropane (8), and (+)-(1S,3S,5R,6S)-merredissine (9)

Dermal mesenchymal stem cells (DMSCs) inhibit skin-homing CD8+ T cell activity, a determining factor of vitiligo patients' autologous melanocytes transplantation efficiency.

We here investigated the efficiency of autologous melanocyte transplantation of 23 vitiligo patients by focusing on perilesional skin homing CD8+ T lymphocytes, and studied the potential effect of dermal mesenchymal stem cells (DMSCs) on CD8+ T cell activities in vitro. Out of 23 patients with the autologous melanocyte transplantation, 12 patients (52.17%) had an excellent re-pigmentation, 6 patients (26.09%) had a good re-pigmentation, 5 patients (21.74%) had a fair or poor re-pigmentation. CD8+ T cells infiltrating was observed in the perilesional vitiligo area of all patients. Importantly, the efficiency of the transplantation was closely associated with skin-homing CD8+ T cell activities. The patients with high number of perilesional CD8+ T cells or high level of cytokines/chemokines were associated with poor re-pigmentation efficiency. For in-vitro experiments, we successfully isolated and characterized human DMSCs and skin-homing CD8+ T cells. We established DMSCs and CD8+ T cell co-culture system, where DMSCs possessed significant inhibitory effects against skin homing CD8+ T lymphocytes. DMSCs inhibited CD8+ T cells proliferation, induced them apoptosis and regulated their cytokines/chemokines production. Our results suggest that vitiligo patients' autologous melanocytes transplantation efficiency might be predicted by perilesional skin-homing CD8+ T cell activities, and DMSCs might be used as auxiliary agent to improve transplantation efficacy

Interferon-γ Induces Senescence in Normal Human Melanocytes

<div><p>Background</p><p>Interferon-γ (IFN-γ) plays an important role in the proceedings of vitiligo through recruiting lymphocytes to the lesional skin. However, the potential effects of IFN-γ on skin melanocytes and the subsequent contribution to the vitiligo pathogenesis are still unclear.</p><p>Objective</p><p>To investigate the effects of IFN-γ on viability and cellular functions of melanocytes.</p><p>Methods</p><p>Primary human melanocytes were treated with IFN-γ. Cell viability, apoptosis, cell cycle melanin content and intracellular reactive oxygen species (ROS) level were measured. mRNA expression was examined by real-time PCR. The release of interleukin 6 (IL-6) and heat shock protein 70 (HSP-70) was monitored by ELISA. β-galactosidase staining was utilized to evaluate melanocyte senescence.</p><p>Results</p><p>Persistent IFN-γ treatment induced viability loss, apoptosis, cell cycle arrest and senescence in melanocytes. Melanocyte senescence was characterized as the changes in pigmentation and morphology, as well as the increase of β-galactosidase activity. Increase of p21^Cip1/Waf1 protein was evident in melanocytes after IFN-γ treatment. IFN-γ induction of senescence was attenuated by siRNAs against p21, Janus kinase 2 (JAK2) or signal transducer and activator of transcription 1 (STAT1), but not by JAK1 siRNA nor by p53 inhibitor pifithrin-α. IFN-γ treatment increased the accumulation of intracellular ROS in melanocytes, while ROS scavenger N-acetyl cysteine (NAC) effectively inhibited IFN-γ induced p21 expression and melanocyte senescence. IL-6 and HSP-70 release was significantly induced by IFN-γ treatment, which was largely inhibited by NAC. The increase of IL-6 and HSP-70 release could also be observed in senescent melanocytes.</p><p>Conclusion</p><p>IFN-γ can induce senescence in melanocytes and consequently enhance their immuno-competency, leading to a vitiligo-prone milieu.</p></div

Effects of IFN-γ on melanogenesis in normal melanocytes.

<p>(A) Melanocytes were treated with various concentrations of IFN-γ (0, 100 or 1000 U/ml) for 3 or 7days before melanin content was measured. The melanin content was normalized on the basis of protein concentration. (b–g) Total RNA was extracted from melanocytes treated with or without IFN-γ for 24 hours. Real-time PCR was then performed to evaluate the relative mRNA levels of (B) tyrosinase (TYR), (C) tyrosinase-related protein 1 (TYRP1), (D) Melan-A, (E) melanocyte protein 17 (PMEL17), (F) microphthalmia-associated transcription factor (MITF), and (G) dopachrome tautomerase (DCT). The values shown represent the mean ± SD of three independent melanocyte cultures. *P<0.05 and **P<0.01.</p